PD5179 Sample Summary

## `summarise()` has grouped output by 'patient', 'age_at_sample_exact', 'age_at_sample', 'DOB', 'DATE_OF_DIAGNOSIS'. You can override using the `.groups` argument.
## Joining, by = "PDID"
patient ID age_at_sample_exact cell_type phase BaitLabel
2 PD5179 PD5179c 35.44422 WGS Recapture c
3 PD5179 PD5179d 44.32854 WGS Recapture d
4 PD5179 PD5179e 48.79671 WGS Recapture e
1 PD5179 COLONY50 49.68104 BFU-E-Colony Colony NA

Tree

tree=plot_basic_tree(PD$pdx,label = PD$patient,style="classic")

Expanded Tree with Node Labels

The nodes in this plot can be cross-referenced with nodes specified in subsequent results. The plot also serves to give an idea of what the topology at the top of the tree looks like.

tree=plot_basic_tree(expand_short_branches(PD$pdx,prop = 0.1),label = PD$patient,style="classic")
node_labels(tree)

Timing of driver mutations (using Model = poisson_tree )

Note that the different colours on the tree indicate the separately fitted mutation rate clades.

Driver Specific Mutation Rates & Telomere Lengths by Colony & Timepoint

## 
## Random-Effects Model (k = 1; tau^2 estimator: REML)
## 
##   logLik  deviance       AIC       BIC      AICc 
##  -0.0000    0.0000    4.0000      -Inf   16.0000   
## 
## tau^2 (estimated amount of total heterogeneity): 0
## tau (square root of estimated tau^2 value):      0
## I^2 (total heterogeneity / total variability):   0.00%
## H^2 (total variability / sampling variability):  1.00
## 
## Test for Heterogeneity:
## Q(df = 0) = 0.0000, p-val = 1.0000
## 
## Model Results:
## 
## estimate      se     zval    pval    ci.lb    ci.ub 
##  18.9207  0.7215  26.2223  <.0001  17.5065  20.3349  *** 
## 
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## `summarise()` has grouped output by 'patient'. You can override using the `.groups` argument.
## `summarise()` has grouped output by 'patient'. You can override using the `.groups` argument.
node driver status child_count type colony_count mean_lambda_rescaled correction sd_rescaled lb_rescaled ub_rescaled median_rescaled p_lt_wt
-1 WT 1 -1 local 3 18.92068 1.155211 0.5206336 17.93460 19.97831 18.90797 NA
97 JAK2,9+ 1 89 local 6 23.39602 1.155211 1.1790889 21.49600 26.07115 23.24817 5.0e-05
98 1q+,9q-:JAK2,9+ 1 83 local 83 23.58796 1.155211 1.2966562 21.36423 26.45578 23.47236 2.5e-05

Driver Acquisition Timeline

All ages are in terms of post conception years. The vertical red lines denote when colonies were sampled and blue lines when targeted follow up samples were taken.

patient node driver child_count lower_median upper_median lower_lb95 lower_ub95 upper_lb95 upper_ub95 N group age_at_diagnosis_pcy max_age_at_sample min_age_at_sample
PD5179 97 JAK2,9+ 89 0.021439 20.47613 0.0117661 0.0466428 18.32146 23.47691 4 JAK2 34.77344 50.40931 36.17248
PD5179 180 1q+ 6 20.476126 21.23976 18.3214562 23.4769087 19.10397 24.17348 4 1q+ 34.77344 50.40931 36.17248
PD5179 98 1q+,9q- 83 20.476126 29.39066 18.3214562 23.4769087 27.34704 31.72855 4 1q+ 34.77344 50.40931 36.17248

Copy Number Variation and Timing

Summary of LOH timing inference

## Timings using the Clade Specific Rates
label node het.sensitivity chr start end nhet nhom mean_loh_event lower_loh_event upper_loh_event t_before_end t_before_end_lower t_before_end_upper kb count_in_bin count_se pmut pmut_se xmean xse_mean xsd x2.5. x50. x97.5. xn_eff xRhat lmean lse_mean patient driver3 child_count
9q- 181 0.9519 9 70484945 141112375 4 0 NA NA NA NA NA NA 70700000 11349 106.5 0.02479 0.0002327 0.2265 0.001151 0.1704 0.008066 0.1907 0.6235 21938 0.9999 5.421 0.0003628 NA NA NA

Duplications?

## Timings using the Clade Specific Rates
label node het.sensitivity chr start end dupcount ndupcount mean_dup_event lower_dup_event upper_dup_event t_before_end t_before_end_lower t_before_end_upper kb count_in_bin count_se pmut pmut_se xmean xse_mean xsd x2.5. x50. x97.5. xn_eff xRhat lmean lse_mean patient driver3 child_count
1q+ 98 0.9996 1 150000000 300000000 3 2 27.71 24.339 29.37 1.728 0.06013 5.094 99300000 15658 125.1 0.03420 0.0002733 0.8043 0.0010348 0.15600 0.4232 0.8425 0.9932 22726 1 5.646 0.0003342 PD5179 1q+,9q-:JAK2,9+ 83
8+ 182 0.9588 8 0 300000000 13 16 NA NA NA NA NA NA 146400000 26546 162.9 0.05798 0.0003558 0.8504 0.0007159 0.09892 0.6276 0.8648 0.9916 19095 1 26.430 0.0012868 NA NA NA
9+ 97 0.9999 9 0 300000000 6 19 10.54 5.232 16.41 10.061 4.18623 15.369 141300000 19318 139.0 0.04219 0.0003035 0.5111 0.0008728 0.13998 0.2531 0.5069 0.7966 25722 1 13.590 0.0006029 PD5179 JAK2,9+ 89

VAF Distribution of Targeted Follow Up Samples

Here we exclude all local CNAs and depict as color VAF plots